Scientists from the University of North Carolina at Chapel Hill have painted the first clear picture of two cellular proteins that can prompt cancer cells to spread. John Sondek and his colleagues describe in today's Nature the three-dimensional crystal structure of a G protein bound to its activator¿a small molecule called guanosine triphosphate (GTP). They hope that being able to see how the proteins interact will help explain how the complex normally functions, and what goes wrong when it contributes to cancer metastasis. Such an understanding could provide new drug targets.
"You can think of a G protein as a light switch," Sondek explains. "And there are many of these proteins in your body that are controlling numerous functions, depending on whether they're switched on or off." The Rho family of G proteins he studied help regulate a cell's shape, division and movement, and chemicals called guanine nucleotide exchange factors (GEFs) can flip their switch. "If GEFs are in their active form, they in turn activate the G protein," Sondek says. "Trouble occurs when you get a perpetual 'on' state for these G proteins, which can lead to malignancies." Using x-ray crystallography techniques, Sondek and his team captured an image of the G protein halfway between "on" and "off." Sondek adds, "Now the question is, can we turn the light switch, or G protein, 'on' and 'off' at will?"